The latest data on the pathogenesis of ulcer disease is presented in this text, with the emphasis that an understanding of the pathogenesis and etiology of ulcer diseases represents the most rational approach to pharmacology - the prevention and treatment of ulcer disease. Early and late biochemical and functional changes, morphologic stages of the injury and healing phases, as well as vascular factors in ulceration are highlighted. In addition, new pathogenetic elements on neuroendocrine and other endogenous modulators and circadian rhythms in ulcerogenesis are covered. The section on new pharmacology consists of several chapters presenting new animal models of gastric, small intestinal and colonic ulcers because in vivo models represent the basis to test and accurately detect new antiulcer drugs. A large series of chapters cover new drugs for ulcer prevention and treatment. This book is indispensible to investigators in basic and applied research, academic and industrial pharmacologists and clinicians in gastroenterology.
Table of Contents
PATHOGENESIS. EARLY AND LATE BIOCHEMICAL AND FUNCTIONAL CHANGES. Mechanisms of Gastrointestinal Damage by Non-Steroidal Anti-inflammatory Drugs. Correlations Between Free Radicals and Membrane-Dependent Energy Systems in Ethanol-Induced Gastric Mucosal Damage in Rats. Gastric Motility and Overall Blood Flow During Cold Restraint in the Rat. Enzymic Aspects of Cysteamine-Induced Duodenal Ulcers with Special Reference to Bicarbonate Secretion. Cysteamine is a Potent Inhibitor of Duodenal Phosphoprotein Phosphatase in Rats: Probable Role of Gastric Acid Hypersecretion. MORPHOLOGIC STAGES OF THE INJURY AND HEALING PHASES. Mechanisms of Rapid Epithelial Restitution of the Superficial Rat Gastric Mucosa after Ethanol Injury. Microscopic Analysis of Ischemic Gastric Injury in the Rat. Effects of Ulcerogens and Other Conditions on Gastric Epithelial Proliferation. Gastric Mucosal Barriers and the Actions of Aspirin. Early Cytologic Precursors to Cysteamine-Induced Duodenal Ulcer in Rats. VASCULAR FACTORS IN ULCERATION. Vascular Factors in Gastric Mucosal Injury. The Role of Microvasculature in Acute Gastric Mucosal Damage and Protection. Gastric Mucosal Microvascular Architecture and Mucosal Blood Flow in Rats During Stress. Role of Acid and Tissue Prostaglandins in the Production of Gastric Mucosal Damage. Critical Mucosal Oxygenation Level and Promotion by Acid and Histamine of Hemorrhagic Shock-Induced Gastric Ulcer in Rats. CENTRAL AND PERIPHERAL NEUROENDOCRINE INFLUENCES. Central Nervous System Action of Neuropeptides to Influence or Prevent Experimental Gastroduodenal Ulceration. Neural Influences on Gastroduodenal HCO3 Secretion. Involvement of Dopamine and Dopamine Receptors in Stress Gastric Ulceration. Somatostatin and Gastrin Secretion from the Isolated Perfused Rat Stomach: Neural and Hormonal Regulation and the Effect of the Ulcerogen, Cysteamine. Possible Involvement of Central Mechanisms in Antiulcer and Antisecretory Actions of Prostaglandins. CIRCADIAN RHYTHMS IN GI FUNCTIONS AND ULCERS. Rhythmic Behavior in the Gastrointestinal Tract. Sex Differences in Circadian Rhythms of Serum Gastrin. Circadian Patterns of Susceptibility to Gastric Mucosal Injury. PHARMACOLOGY. NEW ANIMAL MODELS OF DUODENAL ULCER. Duodenal Ulcers Induced in Dogs by Indomethacin Plus Histamine. The Dopaminergic Neurotoxin 1-Methyl-4-Phenyl 1,2,3,6-Tetrahydropyridine (MPTP) is a New Duodenal Ulcerogen in the Rat. NEW DRUGS FOR ULCER PREVENTION AND TREATMENT. Sucralfate Protection of the Gastric Mucosa Against Ethanol Injury (Prostaglandin Mediated Mechanisms of Action?). Perspectives on the Pharmacology of Misoprostol. The Gastric Antiulcer Effects of Verapamil in Rats. Lidocaine, a Membrane Stabilizer, Affords Gastric and Cardiac Cytoprotection During Acute Gastric Distention in the Dog. Copper Complexes Offer a Physiologic Approach to Treatment of Ulcers. Gastric Cytoprotection by Sulfhydryl Compounds; Partial Dependence on Endogenous Prostaglandins. Recent Data on Inhibition of Mucosal Damage by Pyrido-Pyrimidines. Cytoprotective and Antidiarrheal Effects of Cysteamine, and Mechanistic Role of Sulfhydryls. MECHANISMS OF ACTION. The Use of in vivo and in vitro Markers of Cellular Disruption to Assess Damage and Protection in the Gastrointestinal Tract. On the Mechanisms of Cytoprotection. The Role of Endogenous Nonprotein and Protein Sulfhydryls in Gastric Mucosal Injury and Protection. The Importance of Surface Hydrophobicity to the Barrier Properties of the Stomach. Index.